Elucidation of the principles of formation of the Alzheimer's disease-related complex using nucleotide and peptide tools

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06524
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Nagata Takashi 京都大学, エネルギー理工学研究所, 准教授 (10415250)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: アミロイドβ / プリオン / アプタマー / 繊維化 / NMR

Outline of Final Research Achievements

Our results indicate that the RNA aptamer we previously identified, which binds strongly to the prion protein (PrPC), may reverse the reduction in long-term memory caused by the soluble amyloid-β peptide (Aβ). Additionally, we developed an RNA aptamer with higher performance. We anticipate that these findings will contribute to understanding the mechanisms behind memory and learning impairments. Moreover, because RNA aptamers interact with PrPC differently than anti-PrPC antibodies, they could provide a novel foundation for creating new therapeutic agents. We also utilized our expertise in sample preparation, structural analysis, and analysis of molecular motion by NMR to extend this research to other systems.

Free Research Field

構造生物科学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病に関係するアミロイドβペプチド（Aβ）と狂牛病に関係するプリオン蛋白質（PrPC）の結合が、記憶や学習の障害を引き起こすと考えられている。本研究では、我々が以前取得したPrPCに強く結合するRNAアプタマーが、Aβによる長期記憶の減弱を回復できることを示唆する結果を得た。また、より高性能のアプタマーも取得した。本研究成果は、記憶や学習障害の発生メカニズムの解明と、創薬研究の発展に今後展開させることが出来る。